Patent GB-554303-A (GB)
Title: Manufacture of saturated and unsaturated androstane-17-ol-ones or esters or ethers thereof
IPC: C07J1/00
Filed: 1940-12-23
Abstract: 554,303. Androstane - 17 - - ol - ones. SOC. OF CHEMICAL INDUSTRY IN BASLE. Dec. 23, 1940, Nos. 18028 and 18029. Convention dates, Dec. 29, 1939, and Oct. 31, 1940. [Class 2 (iii)] Saturated or unsaturated androstane 17-olones or esters or ethers thereof are prepared by treating an androstane-17-one containing in 5- position a free, esterified, or etherified hydroxyl group but no other substituent in rings A or B with a reducing agent or metal hydrocarbon compound which is known to convert a-CO- group into a CR(OH) group where R stands for hydrogen or a saturated or unsaturated hydrocarbon residue, then acting on the product with an agent which eliminates water, acid or alcohol and finally treating the unsaturated product with an oxidizing agent known to be suitable for introducing in α-position to a double linkage an oxo-group or a free or esterified hydroxyl group. In the latter case the product is treated with an oxidizing or a dehydrogenating agent to convert a free hydroxyl group in ring A or B into a keto-group, if required after hydrolysis. The treatment of the unsaturated compound formed by the elimination of the 5-hydroxyl group may be modified in that an oxidizing agent is used which is known to be suitable for causing the addition of oxygen or free or esterified hydroxyl group to a double linkage. In this case the product is treated with an agent which causes the elimination of water from free or partially esterified vicinal hydroxy groups, or with an oxidizing or dehydrogenating agent to convert a free hydroxyl group into a keto-group. The 17-carbinol group may be esterified or etherified during or after the above operations. The parent materials for the process of the invention may be prepared as described in Specification 550,478. Agents mentioned as suitable for converting a (-CO-) group into a CR(OH) group include reducing agents and metal hydrocarbon compounds such as Grignard reagents and alkali hydrocarbons. After this first reduction step the 17-carbinol group is protected by esterification or etherification if the oxidizing agent used in the next stage is such as to render this necessary. As esterification agents numerous aliphatic and aromatic acids are mentioned and as etherification agents aliphatic or aliphaticaromatic alcohols may be used. Oxidizing agents mentioned as suitable for introducing an oxo-group include chromic acid, selenium dioxide and the lead tetra-acylates. These lead to the formation of compounds containing in α-position to the double linking a keto-, hydroxyl or esterified hydroxyl group. Oxidizing agents used to add on oxygen or free or esterified hydroxyl groups directly at the double linkage include hydrogen peroxide, alone or in the presence of an alkali or a metal oxide, per acids, halogens, metal oxides such as osmium tetroxide or vanadic acid in some cases in presence of a chlorate, also permanganates and silver halide benzoate complexes. In examples (1) 5-Oxyandrostane-17-one is hydrogenated in alcohol solution in the presence of a nickel catalyst to form androstane-5:17-diol which on heating with propionic anhydride is converted into #<SP>4</SP>-androstene-17-ol-propionate. This is oxidized with chromiun trioxide in glacial acetic acid to testosterone propionate in addition to the corresponding 6-oxo- and 3:4-dioxo-compounds. (2) 5-Chloro-androstane-17-one is treated with methyl magnesium iodide to form 5-chloro-17-methyl androstane-17-ol which on treatment with aqueous hydrochloric acid. forms #<SP>4</SP>-17-methyl-androstene-17-ol. Treatment with chromic acid as in example (1) forms 17-methyl testosterone. Alternatively by the use of selenium dioxide #<SP>4</SP>-17-methyl androstene-3:17-diol may be formed as an intermediate product and converted into 17-methyl testosterone by oxidation.